Brain ; pathology ; Caudate Nucleus ; pathology ; Child, Preschool ; Humans ; Huntingtin Protein ; Huntington Disease ; diagnosis ; genetics ; pathology ; Magnetic Resonance Imaging ; Male ; Nerve Tissue Proteins ; genetics ; Pedigree ; Trinucleotide Repeats ; genetics

OBJECTIVETo preliminarily study the effective dosage range and mechanism of the abirritation of volatile oil of Evodia Fructus on the stomach cold syndrome model in mice, and discuss the correlation between its accompanying toxicity and oxidative damage mechanism, in order to provide the experimental basis for explaining the efficacy-syndrome-toxicity correlation.

METHODThe stomach cold-syndrome model in mice was induced by the classic hot plate test by orally administrating with different doses of volatile oil of Evodia Fructus, in order to observe its abirritation and companying toxic and side effects and detect serum ALT, AST, PGE2, NO, NOS, MDA, SOD, GSH, GSH-Px, BUN, CR and hepatic ALT, AST. The companying toxic symptoms in mice were recorded in toxic reaction integral table.

RESULTVolatile oil of Evodia Fructus had an obvious analgesic effect at 30 min after the oral administration and reached the peak effect at 60 min, with certain "dose-effect" and "time-effect" relations, rises in serum and hepatic ALT and AST levels, serum PGE2, MDA, NO and NOS and hepatic indexes, decreases in SOD, GSH and GSH-Px and no notable change in BUN, CR levels and kidney weight/body ratio. Conclusion: The abirritation mechanism of volatile oil of Evodia Fructus was related to the inhibition of pain transmitter release, peroxidative damage and NO damage, which is accompanied by certain hepatotoxicity, mainly mainly oxidative damage, with a concurrent "dose-time-toxicity" relationship.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Evodia ; chemistry ; toxicity ; Female ; Fruit ; chemistry ; toxicity ; Humans ; Liver ; drug effects ; metabolism ; Mice ; Oils, Volatile ; administration & dosage ; toxicity ; Oxidative Stress ; drug effects ; Stomach ; drug effects ; metabolism ; Stomach Diseases ; drug therapy ; metabolism

The range of effective dose and mechanism of abirritation about water extraction components of Evodiae Fructus on the stomach cold syndrome model in mice were preliminary studied. The method of stomach cold-syndrome model in mice was built, which were administrated with different doses water extraction components of Evodiae Fructus, observing abirritation and toxicity by the classical hot plate method, detecting the level of ALT, AST, PGE2, NO, NOS, MDA, SOD, GSH, GSH-Px, BUN, CR in serum and ALT, AST in hepatic tissue, and recording toxicity symptoms in mice according to the list of relevant toxicity reaction. The water extraction component of Evodiae Fructus has obvious analgesic action after administration 30 min, arriving peak effect after administration 60 min, showing certain "dose-time-toxicity" relationship. ALT and AST levels in mice serum and liver tissue enhanced; PGE2, MDA, NO, NOS enhanced in mice serum; SOD, GSH, GSH-Px reduced; the BUN, CR levels was no significant alteration; liver weight/ body weight enhanced; kidney weight/body weight was no significant alteration. The a irritation mechanism of volatile oil of Evodiae Fructus was connected with suppressing pain transmitters release, per oxidative damage mechanism and NO damage, which also induced hepatotoxicity and the mechanism of hepatotoxicity is main lyoxidative damage, showing certain "dose-time-toxicity" relationship in accordance to hepato-toxicity injury.
Analgesics ; pharmacology ; Animals ; Body Weight ; drug effects ; Chemical and Drug Induced Liver Injury ; etiology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Evodia ; toxicity ; Female ; Medicine, Chinese Traditional ; Mice ; Plant Extracts ; pharmacology ; toxicity

Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over the traditional chemotherapy. However, it is difficult to control the site and stoichiometry of conjugation in mAb, typically resulting in heterogeneous mixtures of ADCs that are difficult to optimize. New methods for site-specific drug attachment allow development of more homogeneous conjugates and control of the site of drug attachment. In this article, the new literature on development of ADCs and site-specific ADCs is reviewed. In addition, we summarized the various strategies in production of site-specific ADCs.
Antibodies, Monoclonal ; chemistry ; Antibody Specificity ; Binding Sites, Antibody ; Immunoconjugates ; chemistry

Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over the traditional chemotherapy. However, it is difficult to control the site and stoichiometry of conjugation in mAb, typically resulting in heterogeneous mixtures of ADCs that are difficult to optimize. New methods for site-specific drug attachment allow development of more homogeneous conjugates and control of the site of drug attachment. In this article, the new literature on development of ADCs and site-specific ADCs is reviewed. In addition, we summarized the various strategies in production of site-specific ADCs.

Adolescent ; Adult ; Antithrombin III Deficiency ; genetics ; Antithrombins ; Female ; Humans ; Male ; Mutation ; Pedigree ; Phenotype

The new generation cyclooxygenase (COX-2) inhibitor could reduce the gastrointestinal side effect of NSAID drugs, but eventually increase the cardiovascular risk, because its selective inhibition of COX-2 induces the imbalance between PGI2 and TXA2 and the reduction of vasodilatory NO. Under pathological conditions, active oxygen species (O2-*2, etc) were used to induce endo- thelial dysfunction, activate NF-κB to induce expressions of pro-inflammatory cytokines IL-1β and TNF-α, increase ET-1, TXA2 with vasoconstrictor effect, reduce PGI2 and NO with vasodilatory effect, generate further oxidative damage together with NO, and reduce the bioavailability of NO. NO-NSAIDs and NO-Coxibs drugs raised the level of NO by introducing NO-donor (ONO2). NSAIDs drugs enhanced the anti-inflammatory activity of COX-2 and reduced gastrointestinal side effects by inhibiting selectively COX-2. If antioxidant structures with active ingredients of traditional Chinese medicines were introduced to improve the antioxidant activity of NSAIDs, they could scavenge the active oxygen species to protect the normal function of vascular endothelia and enhance the bioavailability of NO, which is conducive to enhance the cardiovascular safety of cyclooxygenase (COX-2) inhibitor.
Anti-Inflammatory Agents ; therapeutic use ; Biomarkers, Pharmacological ; Cardiovascular Diseases ; drug therapy ; enzymology ; immunology ; Cyclooxygenase 2 ; immunology ; Cyclooxygenase 2 Inhibitors ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; NF-kappa B ; immunology ; Reactive Oxygen Species ; immunology ; Tumor Necrosis Factor-alpha ; immunology

One strain of Pseudoalteromonas sp. E18 was isolated from the sea mud of Ningbo, Zhejiang. It can produce indigo pigment. The morphological, cultural and biochemical characteristics of the bacterium were studied. The indigo pigment was also extracted. The results showed that the maximum absorption peak of the pigment was at 579nm. The pigment was stable to UV, Na_2SO_3,It was also stable at pH 3～9. The pigment was unstable to the sunlight and high concentration H_2O_2. Temperature of 60℃～80℃ could increase the hue while temperature higher than 90℃ could reduce the hue.

Objective To evaluate the effect s of Ginkgo Leaf Extract and diphyridamole injection on patient s with CKD.Methods 60 patients with CKD were made up with 36 cases in Ⅲ phase and 24 cases in Ⅳ phase.The patients with CKD were given Ginkgo Leaf Extract and diphyridamole injection,20 mL/d,for 15 days.The parameters of clini- cal condition,function of kidney,ALB and blood fat were observed before and after the therapy and the data were ana- lyzed.Results There were 28 cases that clinical condition was better; 24cases no difference; and 8 cases worse.The level of TC and TG were significantly decreased after the therapy,as well as the uric protein quality of 24 hours(P0.05). Conclusion Essential treatment for CKD combined with Ginkgo Leaf Extract and diphyridamole injection can improve nutrition,delay the process of CKD and protect the renal function in patient s with Ⅲ phase.

Objective To analyze the effect of eukaryotic plasmids containing wild (sense) or anti- sense methylenetetrahydrofolate reductase (MTHFR) gene on cell viability and transcription level of tumor related genes in human gastric cancer cell line.Methods Human gastric cancer cell line MKN-45 was cultured.Recombinant plasmids containing wild MTHFR (W) or antisense MTHFR (A) gene, pCMV-W and pCMV-A,were constructed.Then pCMV-W,pCMV-A and pCMV blank plasmid were transfected into MKN45 cells respectively by using lipofect.Cell viability was analyzed by 3-(4,5-bime- thylthiazolyl-2)-2,5-diphenyhetrazolium dromide(MTT).The transcription levels of Dnmt 1,c-myc, p21~(WAF1) and hMLH1 genes were detected by real-time polymerase chain reaction(PCR).Results Cell vi- ability remarkably increased in those transfected with wild MTHFR (P＜0.01),which was contrary to those transfected with antisense MTHFR(P＜0.01).The expression of those tumor related genes mRNAs were all remarkably decreased in the MKN45-W cells in comparison with those in the MKN45-pCMV cells.No significant difference in the expressions of those tumor related genes mRNAs were found between the MKN45 cells transfected with pCMV-A and blank pCMV.Conclusion MTHFR influences cell viability and the expres- sion level of tumor related genes in human gastric cancer cell line MKN45.